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Abstract Details
Plasma GLP-1 and metabolic dynamics during human liver regeneration and their association with posthepatectomy liver failure.
Ammann, Markus (M);Jonas, Jan Philipp (JP);Pereyra, David (D);Santol, Jonas (J);Hackl, Hubert (H);Kalchbrenner, Tamara (T);Laengle, Johannes (J);Podrascanin, Vanja (V);Lehner, Florian (F);Viragos-Toth, Istvan Levente (IL);Hulla, Wolfgang (W);Ruso, Verena (V);Smoot, Rory (R);Laengle, Friedrich (F);Gruenberger, Thomas (T);Assinger, Alice (A);Starlinger, Patrick P (PP);
BACKGROUND: Metabolic regulation is critical during liver regeneration in rodents, but human data are limited. We investigated perioperative dynamics of circulating metabolites and plasma levels of glucagon-like peptide-1 (GLP-1) and GLP-2, in patients undergoing liver resections, exploring their associations with the histological phenotype of metabolic dysfunction-associated steatotic liver disease (MASLD) and posthepatectomy liver failure (PHLF).
METHODS: Eighty-one and 75 patients from two centers between 2012 and 2023 were studied. Targeted quantitative metabolomic assay of 180 circulating metabolites, perioperative GLP-1, GLP-2, and standard lipid parameter level evaluation was employed. An exploratory PHLF prediction model was developed, including GLP-1 as a metabolic parameter.
RESULTS: Significant alterations of 44 metabolites by postoperative day (POD) 1 and 40 by POD5 were observed, mainly among phospholipid species. Unsupervised clustering identified two metabolic clusters, with one encompassing 93% of PHLF patients by POD5 (P<0.001). Standard plasma lipid parameters displayed consistent decrease after hepatectomy, independent from MASLD phenotype, with the lowest levels in PHLF patients. Postoperative GLP-1 and GLP-2 dynamics displayed a reciprocal pattern, indicating adaptive change in secretion. Preoperative GLP-1 levels were significantly increased in PHLF (P=0.02). Furthermore, incorporation of GLP-1 into the established aspartate aminotransferase to platelet ratio index (APRI) + albumin-bilirubin (ALBI) score, improved PHLF prediction [area under the curve (AUC): 0.833, 95% confidence interval (CI): 0.660-0.964].
CONCLUSIONS: Significant metabolic changes occur during human liver resection, particularly in phospholipid metabolism, along with distinct perioperative dynamics of GLP-1 and GLP-2, closely linked to PHLF and independent of the histological phenotype of MASLD. Additionally, we provide exploratory results on the predictive value of GLP-1 for PHLF, emphasizing a holistic model of liver function assessment highlighting the metabolic component of human liver regeneration.
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